Department of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, NY 12180.
Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180.
Proc Natl Acad Sci U S A. 2018 Nov 27;115(48):12188-12193. doi: 10.1073/pnas.1805932115. Epub 2018 Nov 14.
Our understanding of the left-right (LR) asymmetry of embryonic development, in particular the contribution of intrinsic handedness of the cell or cell chirality, is limited due to the confounding systematic and environmental factors during morphogenesis and a ack of physiologically relevant in vitro 3D platforms. Here we report an efficient two-layered biomaterial platform for determining the chirality of individual cells, cell aggregates, and self-organized hollow epithelial spheroids. This bioengineered niche provides a uniform defined axis allowing for cells to rotate spontaneously with a directional bias toward either clockwise or counterclockwise directions. Mechanistic studies reveal an actin-dependent, cell-intrinsic property of 3D chirality that can be mediated by actin cross-linking via α-actinin-1. Our findings suggest that the gradient of extracellular matrix is an important biophysicochemical cue influencing cell polarity and chirality. Engineered biomaterial systems can serve as an effective platform for studying developmental asymmetry and screening for environmental factors causing birth defects.
由于在形态发生过程中存在系统性和环境因素的干扰，以及缺乏生理相关的体外 3D 平台，我们对于胚胎发育左右（LR）不对称性的理解，特别是细胞内在的手性或细胞手性的贡献，受到了限制。在这里，我们报告了一种高效的双层生物材料平台，用于确定单个细胞、细胞聚集体和自发组织的中空上皮球体的手性。这个生物工程龛提供了一个均匀定义的轴，允许细胞自发旋转，并具有顺时针或逆时针的定向偏向。机制研究揭示了一种依赖肌动蛋白的、细胞内在的 3D 手性特性，这种特性可以通过肌动蛋白交联通过 α-辅肌动蛋白-1 来介导。我们的发现表明，细胞外基质的梯度是影响细胞极性和手性的重要生物物理化学线索。工程生物材料系统可以作为研究发育不对称性和筛选导致出生缺陷的环境因素的有效平台。
